This is an open-label phase I study of fostamatinib in combination with ruxolitinib for the treatment of chronic GvHD with a suboptimal response to corticosteroids. The primary objective is to identify a minimum safe and biologically effective dose of fostamatinib when combined with standard of care ruxolitinib for the treatment of steroid refractory and steroid dependent cGVHD. The secondary objective is to estimate the efficacy of the combination of ruxolitinib and fostamatinib for the treatment of steroid refractory and steroid dependent cGVHD.
The target enrollment is 24-30 subjects. The study will begin with an initial dose escalation cohort employing a modified 3+3 design to investigate up to three doses of fostamatinib. Using safety, efficacy, pharmacodynamic (PD), and pharmacokinetic data (PK), an interim assessment will be performed to determine two candidate doses of the biologically optimal dose to investigate further. A safety expansion cohort will be opened to backfill these two candidate doses up to a total 12 patients per dose, including those in the dose escalation cohort who received the candidate doses. Patients will then be randomized to one of these two candidate doses in the expansion. If there is an imbalance in the two expansion cohorts, the remaining patient slots after 1:1 randomization will be sequentially backfilled to a total of 12 patients per cohort. A final analysis of safety, efficacy, and PK/PD data in patients who received the two candidate doses will be conducted to determine a minimum safety and biologically effective dose, which will be the recommended phase II dose (RP2D).
The primary hypothesis is that Fostamatinib combined with ruxolitinib is a safe therapy for and has synergistic activity in cGvHD. The recommended phase II dose will be determined by the study investigators in collaboration with the sponsors. The decision to select the recommended phase II dose will occur only after all patients in the part 1 have completed at least 28 days of therapy. The decision will be based on the valuation of all relevant, available data, and not solely on dose-limiting toxicities.

Start Date01 May 2025

Sponsor / Collaborator

Duke University

[+3]

NCT05509582

/ Enrolling by invitationPhase 2IIT

Extension Study (Extended Access) of Syk-inhibition Using Fostamatinib to Treat Post-Transplant Immune-mediated Cytopenias

Background:
People who have a blood stem cell transplant can sometimes develop cytopenia. This means that their levels of one or more types of blood cell, such as the red cells or platelets, are lower than they should be. This can occur because a person s immune system might attack these cells after a stem cell transplant. Up to 20% of people who have blood stem cell transplants develop cytopenias, which can lead to anemia, severe bleeding, infections, and other problems. Treatments are needed to help keep blood cell levels stable after blood stem cell transplant.
Objective:
To evaluate the long-term effects of a study drug (fostamatinib) in people with cytopenia after a blood stem cell transplant.
Eligibility:
People who responded well to fostamatinib in an earlier study.
Design:
Participants will be screened. They will have a physical exam and blood tests.
Fostamatinib is an oral tablet taken by mouth. Participants will take the pills at the same dose and frequency as they did during the previous study. They will take the pills for up to 21 months. The dosage of the drug may be reduced over time if their blood cell levels are stable.
Participants will have a medical assessment every month. This can be with their local doctor or at the NIH clinic.
Participants will have blood tests every 3 months.
Participants will have a follow-up visit after they stop taking the drug. Their vital signs will be taken, and they will have blood drawn. They will answer questions about their health.

Start Date09 Feb 2025

Sponsor / Collaborator

National Heart, Lung & Blood Institute

NCT06564207

/ Not yet recruitingPhase 2IIT

Randomized, Double-Blinded, Placebo-Controlled Phase 2 Study for the Long Term Evaluation of Fostamatinib for the Treatment of Adult Patients With Acute Respiratory Distress Syndrome (ARDS)

This study is designed to evaluate the safety and efficacy of fostamatinib in hospitalized adult participants with acute respiratory distress syndrome (ARDS).

Start Date01 Feb 2025

Sponsor / Collaborator

Inova Health Care Services

[+2]

100 Clinical Results associated with Fostamatinib Disodium

100 Translational Medicine associated with Fostamatinib Disodium

100 Patents (Medical) associated with Fostamatinib Disodium

574

Literatures (Medical) associated with Fostamatinib Disodium

01 Mar 2025·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

AP2M1 as the potential biomarker for prediction of the response of atopic dermatitis to Dupilumab therapy: Multi-omics analysis and evidence

Article

Author: Yan, Yang ; Peng, Shixiong ; Tang, Qian ; Huang, Xi ; Feng, Hao ; Yan, Wenjie

Many atopic dermatitis (AD) patients have suboptimal responses to Dupilumab therapy. This study identified key genes linked to this resistance using multi-omics approaches to benefit more patients. We selected a prospective cohort of 54 AD treated with Dupilumab from the GEO database. After identifying resistant genes via WGCNA and differential expression analysis, we used machine learning techniques to screen key genes and develop a predictive model. It was found that four key genes (AP2M1, BMP4, DNM1, and RHEB) were identified, showing excellent diagnostic performance for Dupilumab resistance (AUC = 0.832-0.861, P < 0.05) and validated in AD patients via RT-qPCR (P < 0.05). Among them, AP2M1 was significantly correlated with the clinical severity of AD (R = 0.5,P = 0.04) and identified as a potential risk factor (HR = 13.45, 95%CI(1.71-105.65), P = 0.02). The results of immunohistochemistry also revealed overexpression of AP2M1 in AD tissue (P = 0.002). Additionally, immune infiltration analysis suggested that AP2M1-mediated Dupilumab resistance may involve mast cells (R = -0.51, P = 0.02), which also supported by single-cell analysis. And we constructed a regulatory network of AP2M1. Finally, we explored the drug Fostamatinib, targeting AP2M1. In conclusion, AP2M1 may serve as a biomarker for those AD patients exhibiting suboptimal responses to Dupilumab.

01 Feb 2025·INTERNATIONAL IMMUNOPHARMACOLOGY

Fostamatinib alleviates temporomandibular joint osteoarthritis by maintaining cartilage homeostasis through MAPK/NF-κB and AKT/mTOR pathways

Article

Author: Zhang, Dahe ; Yang, Chi ; Xia, Simo ; Shen, Pei ; Zhang, Yuxin ; Xu, Qingyu

Temporomandibular joint osteoarthritis (TMJ OA) is a common degenerative disease characterized by cartilage degeneration. However, the therapeutic strategies aimed to maintain cartilage homeostasis remain unclear. Fostamatinib (Fos) is a potential clinical drug for rheumatoid arthritis (RA) and predicted as target drug for many inflammatory diseases. In this study we investigated the therapeutic effects of Fos for TMJ OA and underlying mechanisms. Interleukin-1β (IL-1β) was used to construct a condylar chondrocyte injury model in vitro and rat TMJ OA models were induced by unilateral anterior crossbite (UAC) in vivo. Subsequently, a series of experiments were performed to assess the therapeutic effects and potential mechanisms of Fos in TMJ OA. Herein, we verified that Fos improved IL-1β-induced decrease in chondrocyte viability and proliferation, as well as inhibited cell apoptosis. Additionally, Fos could alleviate IL-1β-induced inflammation, ECM degradation, and chondrocyte phenotype change through blocking MAPK/NF-κB pathways, as well as promote chondrocyte autophagy by regulating AKT/mTOR pathways. The therapeutic effects of Fos on TMJ OA were further validated through rat UAC model in vivo. Overall, Fos could maintaining cartilage homeostasis through regulating chondrocyte inflammation, ECM degradation, and abnormal cell biological behaviors (apoptosis and autophagy), which made it a promising small molecule drug for TMJ OA early intervention.

01 Feb 2025·INTERNATIONAL IMMUNOPHARMACOLOGY

Spleen tyrosine kinase aggravates intestinal inflammation through regulating inflammatory responses of macrophage in ulcerative colitis

Article

Author: Jin, Guiyuan ; Zhu, Fengqin ; Dong, Guanjun ; Gao, Xizhuang ; Chen, Leilei ; Zhou, Guangxi ; Zhou, Yaqi ; Yang, Yonghong

BACKGROUND:

Ulcerative colitis (UC) is a persistent chronic, non-specific inflammatory disease, and macrophages play a crucial role in its pathogenesis. Spleen tyrosine kinase (Syk) is strongly associated with the pathogenesis of several inflammatory diseases. However, the role of Syk in the pathogenesis of UC is still obscure.

METHODS:

Syk expression was analyzed in peripheral blood mononuclear cells (PBMCs) and colonic tissues of UC patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunofluorescence. A public database was used to analyze the expression of selected signature genes of interest in UC patients with different expressions of Syk. R788, a small molecule inhibitor of Syk, was used to treat macrophages from mice. The functions of macrophages were assessed using qRT-PCR, flow cytometry, and fluorescence microscopy. Dextran sodium sulfate (DSS)-induced colitis mice model was established to determine the role of Syk in UC.

RESULTS:

The Syk levels were markedly increased in PBMCs, colonic tissues, and colonic mucosa lamina propria macrophages from UC patients, and positively related to disease activity. Inhibition of Syk with R788 decreased pro-inflammatory genes expression and increased anti-inflammatory genes expression in peritoneal macrophages and bone marrow macrophages. Blockade of Syk enhanced phagocytosis and bactericidal ability of macrophages. Syk promoted the production of reactive oxygen species of macrophages and M1-type macrophage polarization. Furthermore, inhibition of Syk alleviated intestinal mucosal inflammation in DSS-induced colitis model.

CONCLUSIONS:

Syk plays a vital role in intestinal inflammation by regulating inflammatory responses of macrophages in UC. Targeting Syk may be a promising therapeutic approach for UC.

News (Medical) associated with Fostamatinib Disodium

22 Jan 2025

·www.rigel.com

Rigel's Fostamatinib Being Studied by National Institute of Health in Patients with Sickle Cell Disease

First patient enrolled in NIH/NHLBI-sponsored Phase 1 Study of fostamatinib, Rigel's oral SYK inhibitor SOUTH SAN FRANCISCO, Calif., Jan. 22, 2025 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced the first patient has been enrolled in a Phase 1 study evaluating the safety and tolerability of escalating doses of fostamatinib, the company's oral spleen tyrosine kinase (SYK) inhibitor, in patients with sickle cell disease (SCD). The study is being sponsored by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institute of Health (NIH). Fostamatinib, marketed in the U.S. as TAVALISSE® (fostamatinib disodium hexahydrate) tablets, is approved for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. "Our Phase 1 study evaluating fostamatinib in patients with sickle cell disease is an opportunity to explore a potential new treatment option for a disease that is associated with a high degree of recurrent acute pain events and other acute and chronic potentially life-threatening complications," stated Richard Childs, M.D., scientific director of the NHLBI. "Preclinical research conducted by NIH/NHLBI investigators lead us to believe that SYK inhibition may have the potential to reduce complications related to red cell sickling and thrombo-inflammation in this patient population." "We are excited to support another important study conducted by the NIH/NHLBI for fostamatinib, as they investigate SYK inhibition and its potential to benefit patients with sickle cell disease, a devasting, lifelong condition," said Raul Rodriguez, Rigel's president and CEO. "The study focuses on an area of critical unmet need and contributes to Rigel's mission to improve the lives of patients with hematologic disorders and cancer." This open label Phase 1 dose-escalation study is expected to enroll approximately 20 patients with SCD (NCT05904093). The trial is led by principal investigator Swee Lay Thein, M.D., senior investigator and chief of the Sickle Cell Branch at the NHLBI. Patients will receive oral fostamatinib at a dose of 100 mg twice daily for 14 days, which will be escalated to 150 mg twice daily for an additional 28 days if tolerated. The primary objective of the study is to evaluate the safety and tolerability of fostamatinib. The secondary and exploratory objectives are to assess the mechanism of action of fostamatinib in SCD and mechanistic effects of fostamatinib mediated SYK inhibition on red blood cell membrane integrity and deformability, rate of sickling kinetics, platelet activation and aggregation, and neutrophil activation and neutrophil extracellular trap (NET) formation. The clinical study is being conducted at the NIH Clinical Center in Bethesda, Maryland and is being funded and sponsored by the NIH/NHLBI, with study material provided by Rigel. About SCD & SYK Inhibition Sickle cell disease (SCD) is a genetic hemoglobinopathy that leads to the production of abnormal hemoglobin, the protein that carries oxygen through the body. Normally, red blood cells are disc-shaped and flexible enough to move easily through the blood vessels. In sickle cell disease, red blood cells become rigid and crescent – or "sickle" – shaped, leading to strokes, infections, vaso-occlusive crises (VOC), and multi-organ dysfunction. The condition affects more than 100,000 people in the United States1 and an estimated 7-8 million people worldwide.2 In preclinical studies, R406, the active metabolite of fostamatinib, was shown to inhibit production of neutrophil extracellular traps (NETs) by neutrophils in vitro.3 In a humanized SCD mouse model, R406 treatment significantly decreased platelet ATP secretion and aggregation in response to collagen without a significant effect on bleeding time.4 Fostamatinib could potentially ameliorate SCD-related prothrombic state without an increase in bleeding, addressing an important unmet need. Furthermore, tyrosine phosphorylation of red blood cell (RBC) Band 3 (the anion exchanger 1, of the SLC4A1 gene) compromises the RBC's integrity, leading to shedding of red cell derived microparticles and release of hemoglobin and mitochondrial DNA, key contributors to thrombo-inflammation pathophysiology. By impacting phosphorylation of RBC Band 3 protein, fostamatinib offers the potential for enhanced RBC membrane stability and reduced sickling of RBCs.5 About TAVALISSE® Indication TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Important Safety Information Warnings and Precautions Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required. Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation. Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE. Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation. TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose. Drug Interactions Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose. It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406. Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug. Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug. Adverse Reactions Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%). Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia. Please see www.TAVALISSEUSPI.com for Full Prescribing Information. To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088). TAVALISSE is a registered trademark of Rigel Pharmaceuticals, Inc. Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit www.rigel.com. Forward Looking Statements This press release contains forward-looking statements relating to, among other things, evaluating fostamatinib in patients with sickle cell disease and the potential of SYK inhibition to reduce complications related to red cell sickling and thrombo-inflammation. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "explore", "potential", "may", "expected", "will" and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the development and commercialization of fostamatinib; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law. Contact for Investors & Media: Investors: Rigel Pharmaceuticals, Inc. 650.624.1232 ir@rigel.com Media: David Rosen Argot Partners 646.461.6387 david.rosen@argotpartners.com View original content to download multimedia:https://www.prnewswire.com/news-releases/rigels-fostamatinib-being-studied-by-national-institute-of-health-in-patients-with-sickle-cell-disease-302356919.html SOURCE Rigel Pharmaceuticals, Inc.

Drug ApprovalPhase 1Clinical ResultImmunotherapy

07 Nov 2024

·www.prnewswire.com

Rigel Reports Third Quarter 2024 Financial Results and Provides Business Update

Third quarter total revenue of $55.3 million, which includes TAVALISSE® net product sales of $26.3 million, REZLIDHIA® net product sales of $5.5 million and GAVRETO® net product sales of $7.1 million Entered into an agreement with Kissei to develop and commercialize REZLIDHIA in all potential indications in Japan, the Republic of Korea and Taiwan, recording an upfront cash payment of $10.0 million during the third quarter Initial data from the ongoing Phase 1b study evaluating R289, a dual IRAK1/4 inhibitor, in LR-MDS to be presented at the 66th ASH Annual Meeting Conference call and webcast scheduled today at 4:30 p.m. Eastern Time SOUTH SAN FRANCISCO, Calif., Nov. 7, 2024 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, today reported financial results for the third quarter ended September 30, 2024, including sales of TAVALISSE® (fostamatinib disodium hexahydrate) for the treatment of chronic immune thrombocytopenia (ITP); REZLIDHIA® (olutasidenib) for the treatment of relapsed or refractory (R/R) mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML); and GAVRETO® (pralsetinib) for the treatment of metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) and advanced or metastatic thyroid cancer, and recent business progress. "2024 has been a significant year for Rigel, marked by the acquisition of GAVRETO, our third commercial product, strong revenue growth across our commercial portfolio, and the advancement of our development pipeline," said Raul Rodriguez, Rigel's president and CEO. "This great progress is underpinned by our focus on financial discipline, resulting in positive third-quarter and year-to-date net income. As we close out the year, we will continue driving momentum in our commercial portfolio and hematology and oncology development pipeline." Third Quarter 2024 Business Update Commercial Update Commercial strength continues for all products with record bottles shipped to patients and clinics and total bottles sold. GAVRETO became commercially available from Rigel in June 2024. Third-quarter results reflect the successful transition of existing patients on therapy to Rigel's product. For the fourth quarter, the focus will be on continuing to transition patients. The following table summarizes total bottles shipped for the third quarter: In September, Rigel entered into an exclusive license and supply agreement with Kissei Pharmaceutical Co., Ltd. ("Kissei") to develop and commercialize REZLIDHIA in all potential indications in Japan, the Republic of Korea and Taiwan. Under the terms of the agreement, Rigel received an upfront cash payment of $10.0 million from Kissei, with the potential for up to an additional $152.5 million in development, regulatory and commercial milestone payments. In late October, Rigel issued a Dear Health Care Provider (DHCP) letter related to a new safety signal for GAVRETO after consultation with the U.S. Food and Drug Administration (FDA). The DHCP letter has been posted to the GAVRETO Healthcare Provider website at . Clinical and Development Update Rigel continues to advance its Phase 1b clinical study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of R2891, a novel and selective dual IRAK1/4 inhibitor, in patients with R/R lower-risk myelodysplastic syndrome (LR-MDS). Enrollment in the fifth dose level (500mg / 250mg split dose) is underway. In early November, Rigel announced six poster presentations highlighting data from the company's commercial and clinical-stage hematology and oncology portfolio at the upcoming 66th American Society of Hematology (ASH) Annual Meeting and Exposition. Initial data from the ongoing Phase 1b study evaluating R289 in patients with R/R LR-MDS indicate that R289 was generally well tolerated in a heavily pretreated LR-MDS patient population, the majority of whom were high transfusion burden at study entry. As of the data cutoff, 14 of 19 patients were evaluable for efficacy and per International Working Group (IWG) 2018, RBC-transfusion independence (RBC-TI)/hematologic improvement (HI-E) occurred in 36% of patients receiving R289 doses ≥500 mg QD, with a median duration of RBC-TI of 29 weeks. RBC-TI >24 weeks was achieved in 2 high transfusion burden patients following 3 and 5 prior therapies, including a hypomethylating agent. The company will also present additional data for olutasidenib in patients with R/R mIDH1 AML and MDS. In September, Rigel announced the first patient was enrolled in a Phase 1b/2 triplet therapy trial of decitabine and venetoclax in combination with REZLIDHIA in patients with mIDH1 AML, which is being sponsored and conducted by The University of Texas MD Anderson Cancer Center (MD Anderson). This is the first trial in Rigel's multi-year strategic development alliance with MD Anderson. A paper detailing the differences in molecular structure, binding characteristics and clinical outcomes between olutasidenib and ivosidenib, including response rates in patients previously treated with ivosidenib or venetoclax, was published by Dr. Justin M. Watts, Associate Professor of Medicine, Division of Hematology, Chief, Leukemia Section at the University of Miami Health System, in Current Treatment Options in Oncology in October 2024. Third Quarter 2024 and Year-To-Date Financial Update For the third quarter ended September 30, 2024, total revenues were $55.3 million, consisting of $26.3 million in TAVALISSE net product sales, $5.5 million in REZLIDHIA net product sales, $7.1 million in GAVRETO net product sales, and $16.4 million in contract revenue from collaborations. TAVALISSE net product sales grew 8% compared to $24.5 million in the same period of 2023. REZLIDHIA net product sales grew 107% compared to $2.7 million in the same period of 2023. GAVRETO became commercially available from Rigel in June 2024. Contract revenue from collaborations consisted of $13.0 million from Kissei Pharmaceutical Co., Ltd. (Kissei) related to an upfront fee from sublicensing olutasidenib and delivery of drug supplies, as well as $3.3 million from Grifols S.A. (Grifols) and $0.1 million from Medison Pharma Trading AG (Medison) related to delivery of drug supplies and earned royalties. Total costs and expenses were $41.3 million compared to $32.6 million for the same period of 2023. The increase in costs and expenses was mainly due to higher cost of product sales, driven primarily by increased products sales, a sublicensing revenue fee to Forma, increased royalties and amortization of intangible assets. In addition, there were increases in personnel-related costs and commercial-related expenses. Rigel reported net income of $12.4 million, or $0.71 basic and $0.70 diluted per share, compared to a net loss of $5.7 million, or $0.33 basic and diluted per share, for the same period of 2023. The basic and diluted share and per share amounts for the prior period have been restated to reflect the 1-for-10 reverse stock split effected on June 27, 2024 on a retroactive basis. For the nine months ended September 30, 2024, total revenues were $121.7 million, consisting of $73.8 million in TAVALISSE net product sales, $15.6 million in REZLIDHIA net product sales, $9.0 million in GAVRETO net product sales, and $23.3 million in contract revenue from collaborations. TAVALISSE net product sales grew 8% compared to $68.1 million in the same period of 2023. REZLIDHIA net product sales grew 133% compared to $6.7 million in the same period of 2023. As mentioned above, GAVRETO became commercially available from Rigel in June 2024. Contract revenue from collaborations consisted of $17.5 million from Kissei related to an upfront fee from sublicensing olutasidenib and delivery of drug supplies, as well as $5.5 million from Grifols and $0.2 million from Medison related to delivery of drug supplies and earned royalties. Total costs and expenses were $114.1 million compared to $103.5 million for the same period of 2023. The increase in costs and expenses was mainly due to higher cost of product sales driven primarily by increased products sales, a sublicensing revenue fee to Forma, increased royalties and amortization of intangible assets. In addition, there were increases in personnel-related costs, stock-based compensation expense and commercial-related expenses. These increases were partially offset by decreased research and development costs due to the timing of clinical trial activities related to R289, the company's dual IRAK 1/4 inhibitor program, as well as reduced trial activities related to the completed Phase 3 clinical trials of fostamatinib in patients with COVID-19 and in patients with warm antibody hemolytic anemia (wAIHA). Rigel reported net income of $3.1 million, or $0.18 basic and diluted per share, compared to a net loss of $25.8 million, or $1.49 basic and diluted per share, for the same period of 2023. As discussed above, the share and per share amounts for the prior period have been restated to reflect the 1-for-10 reverse stock split on a retroactive basis for the periods presented. Cash, cash equivalents and short-term investments as of September 30, 2024 was $61.1 million, compared to $49.1 million as of June 30, 2024, and $56.9 million as of December 31, 2023. Conference Call and Webcast with Slides Today at 4:30pm Eastern Time Rigel will hold a live conference call and webcast today at 4:30pm Eastern Time (1:30pm Pacific Time). Participants can access the live conference call by dialing (877) 407-3088 (domestic) or (201) 389-0927 (international). The conference call will also be webcast live and can be accessed from the Investor Relations section of the company's website at . The webcast will be archived and available for replay after the call via the Rigel website. About ITP In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body's own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP. About AML Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 20,800 new cases in the United States, most in adults, in 2024.2 Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need. About NSCLC It is estimated that over 230,000 adults in the U.S. will be diagnosed with lung cancer in 2024. Lung cancer is the leading cause of cancer death in the U.S, with NSCLC being the most common type accounting for 80-85% of all lung cancer diagnoses.5 RET fusions are implicated in approximately 1-2% of patients with NSCLC.6 About TAVALISSE® TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Please click here for Important Safety Information and Full Prescribing Information for TAVALISSE. About REZLIDHIA® REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. Please click here for Important Safety Information and Full Prescribing Information, including Boxed WARNING, for REZLIDHIA. About GAVRETO® GAVRETO is indicated for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).* *Thyroid indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Please click here for Important Safety Information and Full Prescribing Information for GAVRETO. To report side effects of prescription drugs to the FDA, visit or call 1-800-FDA-1088 (800-332-1088). TAVALISSE, REZLIDHIA and GAVRETO are registered trademarks of Rigel Pharmaceuticals, Inc. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit . R289 is an investigational compound not approved by the FDA. The American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Revised June 5, 2024. Accessed June 30, 2024: Leukaemia Care. Relapse in Acute Myeloid Leukaemia (AML). Version 3. Reviewed October 2021. Accessed June 30, 2024: Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood (2015) 126 (3): 319-27. Accessed June 30, 2024. doi: The American Cancer Society. Key Statistics for Lung Cancer. Revised January 29, 2024. Accessed June 30, 2024: Kato, S. et al. RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients. Clin Cancer Res. 2017;23(8):1988-1997 doi: 10.1158/1078-0432.CCR-16-1679 Forward Looking Statements This press release contains forward-looking statements relating to, among other things, expected commercial and financial results, expectations for developing and commercializing REZLIDHIA in certain international markets, study results relating to safety and tolerability of R289 for the treatment of lower-risk myeloid dysplastic syndrome, expectations for development of Rigel's commercial portfolio and hematology and oncology pipeline, and expectations for Rigel's partnering and collaboration efforts. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "plan", "potential", "may", "look to", "expects", "will", "initial", and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the commercialization and marketing of fostamatinib, olutasidenib and pralsetinib; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib, pralsetinib or olutasidenib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib, pralsetinib or olutasidenib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law. Contact for Investors & Media: Investors: Rigel Pharmaceuticals, Inc. 650.624.1232 [email protected] Media: David Rosen Argot Partners 646.461.6387 [email protected] SOURCE Rigel Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

License out/inClinical ResultPhase 1Drug ApprovalASH

05 Nov 2024

·www.prnewswire.com

Rigel Announces Six Poster Presentations at the 66th American Society of Hematology Annual Meeting and Exposition

- Initial data from the ongoing Phase 1b study evaluating R289, a dual IRAK1/4 inhibitor, in LR-MDS - Additional data for REZLIDHIA® (olutasidenib) in patients with mIDH1 AML and MDS SOUTH SAN FRANCISCO, Calif., Nov. 5, 2024 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, today announced upcoming presentations of six posters highlighting data from their commercial and clinical-stage hematology-oncology portfolio at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 7-10, 2024, in San Diego, California and virtually. Rigel's presentations will include data from the ongoing Phase 1b dose escalation/expansion study evaluating R2891, a potent and selective dual inhibitor of IRAK1 and IRAK4, in patients with lower-risk myelodysplastic syndrome (LR-MDS) who are relapsed or refractory (R/R) to prior therapies; REZLIDHIA® (olutasidenib) for the treatment of R/R mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML); and TAVALISSE® (fostamatinib disodium hexahydrate) for the treatment of chronic immune thrombocytopenia (ITP). "We look forward to the presentation of posters at ASH from across our product portfolio. We are very encouraged by the preliminary safety and efficacy data from our ongoing Phase 1b study of R289 in lower risk MDS. R289 was generally well tolerated and demonstrated responses in heavily pretreated LR-MDS patients, a population with a critical unmet need," said Raul Rodriguez, Rigel's president and CEO. "In addition, data from olutasidenib will be presented that adds to the growing body of evidence showing the benefits of its use in patients with mIDH1 AML." ASH Annual Meeting abstracts may be accessed online at . Details of the poster presentations and publications, which will be available in the poster hall and via the virtual event platform, are as follows: Abstract #: 4595 Title: R289, a Dual IRAK 1/4 Inhibitor, in Patients with Relapsed/Refractory (R/R) Lower-Risk Myelodysplastic Syndrome (LR-MDS): Initial Results from a Phase 1b Study Presenter: Guillermo Garcia-Manero, M.D. Time: Monday, December 9, 2024, 6:00pm to 8:00pm PT Initial data from the dose escalation phase using a July 15, 2024 data cutoff date indicate that R289 was generally well tolerated in a heavily pretreated LR-MDS patient population (median number of prior therapies was 4; 79% had received an hypomethylating agent), the majority of whom were high transfusion burden (received ≥8 units red blood cells in 16 weeks prior to enrollment) at study entry. Fourteen of 19 patients were evaluable for efficacy (received ≥1 dose of study drug with ≥1 efficacy assessment). Per International Working Group (IWG) 2018, RBC-transfusion independence (RBC-TI)/hematologic improvement (HI-E) occurred in 36% of patients receiving R289 doses ≥500 mg QD, with a median duration of RBC-TI of 29 weeks (range 12.4-35.9 weeks). RBC-TI >24 weeks was achieved in 2 high transfusion burden patients following 3 and 5 prior therapies, including a hypomethylating agent. Updated data as of October 25, 2024 data cutoff will be presented during the poster session. Abstract #: 1514 Title: Time to Response and Overall Survival in Patients with mIDH1 Relapsed/Refractory Acute Myeloid Leukemia Treated with Olutasidenib Presenter: Stéphane de Botton, M.D., Ph.D. Time: Saturday, December 7, 2024, 5:30pm to 7:30pm PT Results show that while some patients with mIDH1 R/R AML achieve response to olutasidenib very quickly, within 1-2 months of treatment, other patients responded after 6 months of treatment for complete remission (CR) plus CR with partial hematologic recovery (CRh) and up to 10 months for overall response. These results support the prescribing information that suggests treating for at least 6 months to allow time for clinical response in patients without disease progression or unacceptable toxicity. A Cox regression model showed no significant association between time to response and overall survival in the overall responders and those with a CR/CRh response. Abstract #: 2886 Title: Combination of Olutasidenib and Azacitidine Induces Durable Complete Remissions in mIDH1 Acute Myeloid Leukemia: A Multicohort Open-Label Phase 1/2 Trial Presenter: Jorge E. Cortes, M.D. Time: Sunday, December 8, 2024, 6:00pm to 8:00pm PT Olutasidenib plus azacitidine induced high response rates and durable remissions with a tolerable side effect profile in patients with R/R mIDH1 AML, in the first reported analysis of a combination therapy with an mIDH1 inhibitor and a hypomethylating agent focused on the R/R AML setting. CR/CRh was achieved in 31% (21/67) of patients and median duration of CR/CRh was 15 months. Abstract #: 4600 Title: Olutasidenib Alone or in Combination with Azacitidine in Patients with mIDH1 Myelodysplastic Syndromes/Neoplasms: Final 5-Year Data Presenter: Jorge E. Cortes, M.D. Time: Monday, December 9, 2024, 6:00pm to 8:00pm PT Olutasidenib demonstrated encouraging response rates with durable remissions and an acceptable and manageable safety profile in patients with intermediate to very high-risk mIDH1 MDS treated with olutasidenib monotherapy or in combination with azacitidine. In a sub analysis of the 19 efficacy evaluable patients, 79% (11/14) of patients responded to combination therapy and 40% (2/5) responded to monotherapy, which included both patients (2/2) using the approved dose of 150 mg BID olutasidenib. Abstract #: 1525 Title: Effectiveness of Olutasidenib Versus Ivosidenib in Patients with Mutated Isocitrate Dehydrogenase 1 Acute Myeloid Leukemia Who Are Relapsed or Refractory to Venetoclax: The 2102-HEM-101 Trial Versus a US Electronic Health Record-Based External Control Arm Presenter: Catherine E. Lai, M.D. Time: Sunday, December 8, 2024, 6:00pm to 8:00pm PT This study provides the first evidence suggesting favorable effectiveness of olutasidenib versus ivosidenib in patients with mIDH1 AML who were R/R to a venetoclax-based regimen. As with any real-world experience study, limitations include risk of unmeasured confounding and differential outcome reporting. Abstract #: 5080 Title: Real-World Experience with Combination Therapy of Fostamatinib and Thrombopoetin Receptor Agonists (TPO-RAs) for Treatment of Immune Thrombocytopenia (ITP): Patient-Reported Outcomes Presenter: Elizabeth Bowhay-Carnes, M.D. Time: Monday, December 9, 2024, 6:00pm to 8:00pm PT This real-world study treating patients with fostamatinib and a thrombopoetin receptor agonist (TPO-RA) demonstrated that the combination led to a clinically meaningful response in a majority of patients with ITP. ASH Publication Abstract #: 7908 Title: Treatment Patterns and Outcomes of Olutasidenib in Patients with Relapsed/Refractory (R/R) mutated IDH1 Acute Myeloid Leukemia (AML) in the Real World Authors: Aaron Sheppard, Ph.D.; Lixia Wang, Ph.D.; Ravi Potluri, MBA; Eros Papademetriou, MA About R289 R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.2 About AML Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 20,800 new cases in the United States, most in adults, in 2024.3 Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.4 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.5 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need. About ITP In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body's own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP. About REZLIDHIA® INDICATION REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Differentiation Syndrome REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis. If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence. Hepatotoxicity REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin. Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity. ADVERSE REACTIONS The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis. DRUG INTERACTIONS Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers. Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs. LACTATION Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose. GERIATRIC USE No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age. HEPATIC IMPAIRMENT In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome. Click here for Full Prescribing Information, including Boxed WARNING. To report side effects of prescription drugs to the FDA, visit or call 1-800-FDA-1088 (800-332-1088). About TAVALISSE® Indication TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Important Safety Information Warnings and Precautions Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required. Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation. Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE. Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation. TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose. Drug Interactions Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose. It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406. Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug. Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug. Adverse Reactions Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%). Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia. Please see for Full Prescribing Information. To report side effects of prescription drugs to the FDA, visit or call 1-800-FDA-1088 (800-332-1088). REZLIDHIA and TAVALISSE are registered trademarks of Rigel Pharmaceuticals, Inc. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit . R289 is an investigational compound not approved by the FDA. Sallman DA et al. Unraveling the Pathogenesis of MDS: The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype. Front Oncol. June 16, 2016. Accessed September 30, 2024. DOI: The American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Revised June 5, 2024. Accessed September 30, 2024: Leukaemia Care. Relapse in Acute Myeloid Leukaemia (AML). Version 3. Reviewed October 2021. Accessed September 30, 2024: Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood (2015) 126 (3): 319-27. Accessed September 30, 2024. doi: Forward-Looking Statements This press release contains forward-looking statements relating to, among other things, clinical information regarding studies of Rigel's products, including; the progress of the Phase 1b clinical trial of R289 for the treatment of lower-risk myeloid dysplastic syndrome; olutasidenib as a treatment for mIDH1 Relapsed/Refractory Acute Myeloid Leukemia, use of olutasidenib with azacitidine, and use of olutasidenib versus ivosidenib; and, fostamatinib in combination with thrombopoetin receptor agonists for treatment of immune thrombocytopenia, and fostamatinib as early treatment of immune thrombocytopenia. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "plan", "potential", "may", "look to", "expects", "will" and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the commercialization and marketing of fostamatinib, olutasidenib and pralsetinib; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib, pralsetinib or olutasidenib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib, pralsetinib or olutasidenib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law. Contact for Investors & Media: Investors: Rigel Pharmaceuticals, Inc. 650.624.1232 [email protected] Media: David Rosen Argot Partners 646.461.6387 [email protected] SOURCE Rigel Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 1ASH

100 Deals associated with Fostamatinib Disodium

External Link

KEGG	Wiki	ATC	Drug Bank
D09348	Fostamatinib Disodium	B02BX09	DB12010

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Purpura, Thrombocytopenic, Idiopathic	US	Rigel Pharmaceuticals, Inc.	17 Apr 2018
Thrombocytopenia	US	Rigel Pharmaceuticals, Inc.	17 Apr 2018

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Chronic idiopathic thrombocytopenic purpura	NDA/BLA	KR	JW PHARMACEUTICAL Corp.	-
COVID-19	Phase 3	US	Rigel Pharmaceuticals, Inc.	25 Mar 2021
COVID-19	Phase 3	AR	Rigel Pharmaceuticals, Inc.	25 Mar 2021
COVID-19	Phase 3	BR	Rigel Pharmaceuticals, Inc.	25 Mar 2021
COVID-19	Phase 3	MX	Rigel Pharmaceuticals, Inc.	25 Mar 2021
Severe Acute Respiratory Syndrome	Phase 3	US	Rigel Pharmaceuticals, Inc.	25 Mar 2021
Severe Acute Respiratory Syndrome	Phase 3	AR	Rigel Pharmaceuticals, Inc.	25 Mar 2021
Severe Acute Respiratory Syndrome	Phase 3	BR	Rigel Pharmaceuticals, Inc.	25 Mar 2021
Severe Acute Respiratory Syndrome	Phase 3	MX	Rigel Pharmaceuticals, Inc.	25 Mar 2021
Autoimmune Haemolytic Anaemias	Phase 3	US	Rigel Pharmaceuticals, Inc.	24 Apr 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04924660 (NECTAR, CTgov)	Phase 2/3	Thrombosis \| COVID-19 \| Thrombophilia	1,060	TXA127 (TXA127 (4/20/2022 Arm Closed to Accrual))	raeqzefdrz(kgihgogevt) = egbfvmauqm fllcudvblo (skilbccvih, aidmnmzzjt - epngzaenml) View more	-	22 Jan 2025
				TRV027 (TRV027 (4/20/2022 Arm Closed to Accrual))	raeqzefdrz(kgihgogevt) = ohdbhwgwqv fllcudvblo (skilbccvih, fpisnziapw - kwvheyewkf) View more
ASH2024 Manual	Not Applicable	Purpura, Thrombocytopenic, Idiopathic	113	Fostamatinib + TPO-RA	okspyheelb(liripbqjoz) = xsatbdaulo xdhpwbfqnp (ipkjfbdlni ) View more	Positive	09 Dec 2024
2555Early Treatment Use of Fostamatinib (ASH2024)	Not Applicable	Purpura, Thrombocytopenic, Idiopathic Second line	157	Fostamatinib	agtahtfwkl(gcjvykvvhp) = vcuwiafboo kwhkoeehpz (phpofctwgo ) View more	Positive	08 Dec 2024
ASH2024	Not Applicable	Townes-Brocks Syndrome	-	Fostamatinib 3g/kg for 14 days	jrdsdicmtc(jimhqtgweu) = ehvdokepjr gnwnnvsfqm (rksgcdjvav ) View more	-	07 Dec 2024
				Fostamatinib 3g/kg for 7 days	jrdsdicmtc(jimhqtgweu) = boumfqywfb gnwnnvsfqm (rksgcdjvav ) View more
NCT04924660 (Pubmed \| JAMA Netw Open)	Phase 3	Thrombosis \| COVID-19 \| Thrombophilia SARS-CoV-2 infection	400	Fostamatinib 150 mg	elytxetqcn(axkmiqqjue) = vpsmxqokty mbdckqwcuk (dusyetxuzr, 12.4) View more	Negative	03 Dec 2024
				Placebo	elytxetqcn(axkmiqqjue) = mpeailrkiq mbdckqwcuk (dusyetxuzr, 12.1) View more
NCT05593770 (ACTIV-4 \| NECTAR, CTgov)	Phase 2/3	Thrombosis \| COVID-19 \| Thrombophilia	28	Fostamatinib (Fostamatinib)	jrmcmjbjsx(rdccbhcnxi) = kugyrlndvp rfnsruxkjc (zatgokwnww, ukhaxpvpbm - oiruvjgomn) View more	-	05 Nov 2024
				Placebo (Placebo)	jrmcmjbjsx(rdccbhcnxi) = sugstfssoj rfnsruxkjc (zatgokwnww, lfqcsigcdx - wzbatwjrwe) View more
NCT03246074 (CTgov)	Phase 1	Ovarian Cancer	35	Fostamatinib 100 mg bid+Paclitaxel (Fostamatinib 100 mg Bid and Paclitaxel)	brruyazhoh(vwtpxvatpd) = djhoyoxspg eiypjmrkob (fiqdrfhhti, olmutjrxce - ifvjhhouss) View more	-	19 Sep 2024
				Fostamatinib 150 mg bid+Paclitaxel (Fostamatinib 150 mg Bid and Paclitaxel)	brruyazhoh(vwtpxvatpd) = nziogbisyj eiypjmrkob (fiqdrfhhti, zkrfsuthws - bliiytqerv) View more
FIT-1 and FIT-2 (EHA2024)	Not Applicable	Purpura, Thrombocytopenic, Idiopathic	72	Fostamatinib	djmuyoiepj(bhzkssfyie) = diarrhea (n=9), hypertension (n=8), transaminitis (n=7), venous thrombotic event, COVID-19 infection, neutropenia uyzehypezx (hdrmycjgly ) View more	Positive	14 May 2024
EHA2024	Not Applicable	-	-	Fostamatinib	kyxevjoebz(dxntuueudl) = irlozgbozw phszqppnci (pinjcvuqhp )	-	14 May 2024
FOSTAMES (EHA2024)	Not Applicable	Purpura, Thrombocytopenic, Idiopathic	138	Fostamatinib (Tavlesse®)	yvdbwypsln(jdmodscwcr) = kbazaoibxb frsgqhnhjn (otgpmzjrfs ) View more	Positive	14 May 2024

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